Anti-lag3 antibody, conjugate, isolated nucleic acid molecule, vector, host cell, method of preparing Anti-lag3 antibody, pharmaceutical composition, combination product, use of Anti-lag3 antibody and method for treating or preventing a tumor

Description

1 / 52 “ANTI-LAG3 ANTIBODY, CONJUGATE, ISOLATED NUCLEIC ACID MOLECULE, VECTOR, HOST CELL, METHOD FOR PREPARING THE ANTI-LAG3 ANTIBODY, PHARMACEUTICAL COMPOSITION, COMBINED PRODUCT, USE OF THE ANTI-LAG3 ANTIBODY AND METHOD FOR TREATING OR PREVENTING A TUMOR” Cross-reference to related orders

[001] This application is based on and claims priority over Chinese Patent Application No. CN202310327266.6, filed on March 29, 2023, which is incorporated herein by reference in its entirety. Field of invention

[002] This disclosure relates to the field of biomedicine and concerns an anti-LAG3 antibody, a pharmaceutical composition comprising an anti-LAG3 antibody or an antigen-binding fragment thereof, and its use. Background of the Invention

[003] Tumors, especially malignant tumors, are a serious disease that threatens health in the world today and is the second leading cause of death among various diseases. In recent years, the incidence of the disease has increased significantly. Malignant tumors are characterized by low therapeutic effect, a high rate of late metastasis, and a poor prognosis. Although conventional treatment methods (such as radiotherapy, chemotherapy, and surgical treatment) currently adopted clinically significantly alleviate pain and prolong survival time, these methods have major limitations, and it is difficult to further improve their effectiveness.

[004] The lymphocyte activating gene 3 (LAG3), or CD223, is a type I transmembrane protein composed of 498 amino acids and a member of the immunoglobulin superfamily (IgSF). LAG3 is primarily expressed on activated CD4+ and CD8+ T cells. Additionally, it is found in cells such as cells Petition 870250099319, dated 10 / 30 / 2025, p. 11 / 80 LAG3 is also expressed in 2 / 52 natural killer (NK) cells, B cells, regulatory T cells (Tregs), and plasmacytoid dendritic cells (pDCs). (Ruffo Elisa, Wu Richard C, Bruno Tullia C et al. Lymphocyte activation gene 3 (LAG3): The next immune checkpoint receptor. [J]. Semin Immunol, 2019, 42: 101305).

[005] The LAG3 molecule gene is located on human chromosome 12 (12p13.3), adjacent to the CD4 molecule gene, and both share the same exons and introns. The LAG3 molecule and the CD4 molecule exhibit a high degree of structural similarity, although the amino acid sequence homology between the two is only about 20%. Major histocompatibility complex class II (MHC-II) molecules, hepatic sinusoidal endothelial cell lectin (LSECtin) molecules, and galectin-3 molecules are related ligands for the LAG3 molecule. MHC-II molecules are the main ligands for LAG3. The affinity (Kd: 60 nmokL-1) of LAG3 molecules for MHC-II molecules is 100 times greater than that of CD4 molecules, indicating that LAG3 molecules can effectively compete with CD4 molecules for binding to MHC-II molecules and inhibit T cell activation.

[006] In the tumor microenvironment, the expression of the immunosuppressive molecule LAG3 can be detected 24 hours after T cell activation, leading to T cell dysfunction or apoptosis. The LAG3 molecule, through its D1 domain (which contains a proline-rich loop structure), forms a dimeric molecule to specifically bind to the MHC-II molecule in the first signaling axis of CD4+ T cell activation, CD3-TCRMHC-II, so that, in one aspect, a signal transduction pathway for T cell activation is blocked and, in another aspect, an intracellular segment of the LAG3 molecule (KIEELE motif) generates an immunosuppressive signal to negatively regulate CD4+ T cell activity. The LAG3 molecule can promote Treg cell differentiation, participate in signaling to Petition 870250099319, dated 10 / 30 / 2025, page 12 / 80 3 / 52 downstream of the signal transducer and activator of transcription 5 and thus increase the inhibitory effect of Treg cells. This is one of the mechanisms by which tumors escape death by the immune system (Andrews Lawrence P, Marciscano Ariel E, Drake Charles G, et al., LAG3 (CD223) as a target for immunotherapy against cancer. [J]. Immunol Rev, 2017, 276: 80-96).

[007] Several studies have demonstrated that LAG3 is overexpressed in tumor-infiltrating CD8+ T cells of various malignant tumors. For example, in ovarian cancer, tumor-infiltrating CD8+ T cells specific for New York esophageal squamous cell carcinoma antigen 1 (NY-ESO-1) express high levels of PD-1 and LAG3 and have a reduced capacity to produce IFN-γ and TNF-α, leading to lymphocyte inactivation. Galectin-3 and LSECtin interact primarily with LAG3 to regulate CD8+ T cell activation and function. Furthermore, melanoma antigen-specific T cells isolated from patients with metastatic melanoma show a significant upregulation in the expression of LAG3 and other immune checkpoint molecules CTLA-4 and TIM-3. (Liu Hao, Li Xinying, Luo Longlong et al.), Advances in research on the biological function of the lymphocyte activating gene 3 (LAG-3) molecule and clinical application of drugs with antibodies targeting LAG-3 [J]. Chinese Journal of Pharmacology and Toxicology, 2019, 33(01): 70-78).

[008] Currently, several drugs with LAG3 antibodies have entered the clinical research phase, among which Relatlimab, from Bristol Myers Squibb, is the one that has progressed the most, with 10 clinical studies underway. The vast majority of these studies involve combination therapy of Relatlimab with nivolumab for the treatment of tumors such as hematological malignancies, melanoma, glioblastoma, renal cell carcinoma, non-small cell lung cancer and similar cancers.

[009] Currently, there is a need to develop a new Petition 870250099319, dated 10 / 30 / 2025, page 13 / 80 4 / 52 medication with anti-LAG3 antibodies. Brief Description of the Invention

[010] Through intensive studies and creative efforts, the inventors obtained an anti-LAG3 antibody. The inventors surprisingly discovered that the present disclosure's anti-LAG3 antibody (also referred to as the antibody or present disclosure antibody, for short) has superior affinity and / or specificity and is comparable to or even better than that of the positive control antibody (such as Relatlimab) in one or more respects. The present disclosure is detailed below: One aspect of the present disclosure relates to an anti-LAG3 antibody or an antigen-binding fragment thereof, wherein the anti-LAG3 antibody comprises a variable heavy chain region and a variable light chain region, the variable heavy chain region comprising HCDR1, HCDR2 and HCDR3, and the variable light chain region comprising LCDR1, LCDR2 and LCDR3, wherein: HCDR1 comprises an amino acid sequence presented in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence shown in SEQ ID NO: 10, and HCDR3 comprises an amino acid sequence shown in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 12 or SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13 or SEQ ID NO: 15, and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14 or SEQ ID NO: 16.

[011] In some forms of carrying out this disclosure, it is Petition 870250099319, dated 10 / 30 / 2025, p. 14 / 80 5 / 52 provided the anti-LAG3 antibody or its antigen-binding fragment, wherein: The amino acid sequence of HCDR1 is shown in SEQ ID NO: 9, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 11. The amino acid sequence of LCDR1 is shown in SEQ ID NO: 12 or SEQ ID NO: 17, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 13 or SEQ ID NO: 15, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 14 or SEQ ID NO: 16.

[012] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13, and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14; or LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 15, and Petition 870250099319, dated 10 / 30 / 2025, p. 15 / 80 6 / 52 LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 16; or LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 15 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14; or LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 16; or LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 15 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14; or LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13, and Petition 870250099319, dated 10 / 30 / 2025, p. 16 / 80 7 / 52 LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14; or LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13, and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 16; or LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 15 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 16.

[013] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, in which: The amino acid sequence of LCDR1 is shown in SEQ ID NO: 12, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 13, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 14; or the amino acid sequence of LCDR1 is shown in SEQ ID NO: 12, Petition 870250099319, dated 10 / 30 / 2025, p. 17 / 80 8 / 52 The amino acid sequence of LCDR2 is shown in SEQ ID NO: 15 and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 16; or the amino acid sequence of LCDR1 is shown in SEQ ID NO: 17, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 15, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 14; or the amino acid sequence of LCDR1 is shown in SEQ ID NO: 12, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 13, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 16; or the amino acid sequence of LCDR1 is shown in SEQ ID NO: 12, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 15, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 14; or the amino acid sequence of LCDR1 is shown in SEQ ID NO: 17, Petition 870250099319, dated 10 / 30 / 2025, p. 18 / 80 9 / 52 The amino acid sequence of LCDR2 is shown in SEQ ID NO: 13, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 14; or the amino acid sequence of LCDR1 is shown in SEQ ID NO: 17, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 13, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 16; The amino acid sequence of LCDR1 is shown in SEQ ID NO: 17, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 15, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 16.

[014] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: HCDR1 comprises an amino acid sequence shown in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence shown in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence shown in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence presented Petition 870250099319, dated 10 / 30 / 2025, p. 19 / 80 10 / 52 in SEQ ID NO: 12, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14.

[015] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: HCDR1 comprises an amino acid sequence shown in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence shown in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence shown in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 15 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 16.

[016] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: HCDR1 comprises an amino acid sequence shown in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence shown in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence presented Petition 870250099319, dated 10 / 30 / 2025, p. 20 / 80 11 / 52 in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 15 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14.

[017] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: HCDR1 comprises an amino acid sequence shown in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence shown in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence shown in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 16.

[018] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: HCDR1 comprises an amino acid sequence shown in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence presented Petition 870250099319, dated 10 / 30 / 2025, p. 21 / 80 12 / 52 in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence shown in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 15, and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14.

[019] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: HCDR1 comprises an amino acid sequence shown in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence shown in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence shown in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 14.

[020] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: HCDR1 comprises an amino acid sequence presented Petition 870250099319, dated 10 / 30 / 2025, p. 22 / 80 13 / 52 in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence shown in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence shown in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 13 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 16.

[021] In some embodiments of this disclosure, anti-LAG3 antibody or an antigen-binding fragment thereof is provided, wherein: HCDR1 comprises an amino acid sequence shown in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence shown in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence shown in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprises an amino acid sequence shown in SEQ ID NO: 15 and LCDR3 comprises an amino acid sequence shown in SEQ ID NO: 16.

[022] In some embodiments of the present disclosure, the anti-LAG3 antibody or the antigen-binding fragment of Petition 870250099319, dated 10 / 30 / 2025, p. 23 / 80 14 / 52 same, where the amino acid sequence of HCDR1 is shown in SEQ ID NO: 9, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, the amino acid sequence of HCDR3 is shown in SEQ ID NO: 11; The amino acid sequence of LCDR1 is shown in SEQ ID NO: 12, The amino acid sequence of LCDR2 is shown in SEQ ID NO: 13, and The amino acid sequence of LCDR3 is shown in SEQ ID NO: 14.

[023] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, in which: The amino acid sequence of HCDR1 is shown in SEQ ID NO: 9, The amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, The amino acid sequence of HCDR3 is shown in SEQ ID NO: 11; The amino acid sequence of LCDR1 is shown in SEQ ID NO: 12, The amino acid sequence of LCDR2 is shown in SEQ ID NO: 15, and The amino acid sequence of LCDR3 is shown in SEQ ID NO: 16. Petition 870250099319, dated 10 / 30 / 2025, p. 24 / 80 15 / 52

[024] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, in which: The amino acid sequence of HCDR1 is shown in SEQ ID NO: 9, The amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, The amino acid sequence of HCDR3 is shown in SEQ ID NO: 11; The amino acid sequence of LCDR1 is shown in SEQ ID NO: 17, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 15, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 14.

[025] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, in which: The amino acid sequence of HCDR1 is shown in SEQ ID NO: 9. The amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, The amino acid sequence of HCDR3 is shown in SEQ ID NO: 11; The amino acid sequence of LCDR1 is shown in SEQ ID NO: 12, The amino acid sequence of LCDR2 is shown in SEQ ID NO: 13, and Petition 870250099319, dated 10 / 30 / 2025, p. 25 / 80 16 / 52 The amino acid sequence of LCDR3 is shown in SEQ ID NO: 16.

[026] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The amino acid sequence of HCDR1 is shown in SEQ ID NO: 9, The amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, The amino acid sequence of HCDR3 is shown in SEQ ID NO: 11; The amino acid sequence of LCDR1 is shown in SEQ ID NO: 12, The amino acid sequence of LCDR2 is shown in SEQ ID NO: 15, and The amino acid sequence of LCDR3 is shown in SEQ ID NO: 14.

[027] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The amino acid sequence of HCDR1 is shown in SEQ ID NO: 9, The amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, The amino acid sequence of HCDR3 is shown in SEQ ID NO: 11; The amino acid sequence of LCDR1 is shown in SEQ ID NO: 17, Petition 870250099319, dated 10 / 30 / 2025, p. 26 / 80 17 / 52 The amino acid sequence of LCDR2 is shown in SEQ ID NO: 13, and The amino acid sequence of LCDR3 is shown in SEQ ID NO: 14.

[028] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The amino acid sequence of HCDR1 is shown in SEQ ID NO: 9, The amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, The amino acid sequence of HCDR3 is shown in SEQ ID NO: 11; The amino acid sequence of LCDR1 is shown in SEQ ID NO: 17, The amino acid sequence of LCDR2 is shown in SEQ ID NO: 13, and The amino acid sequence of LCDR3 is shown in SEQ ID NO: 16.

[029] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The amino acid sequence of HCDR1 is shown in SEQ ID NO: 9, The amino acid sequence of HCDR2 is shown in SEQ ID NO: 10, The amino acid sequence of HCDR3 is shown in SEQ ID NO: 11; Petition 870250099319, dated 10 / 30 / 2025, p. 27 / 80 18 / 52 The amino acid sequence of LCDR1 is shown in SEQ ID NO: 17, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 15, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 16.

[030] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The variable region of the heavy chain of the anti-LAG3 antibody comprises an amino acid sequence shown in SEQ ID NO: 2, and the variable region of the light chain comprises an amino acid sequence shown in SEQ ID NO: 4; The variable region of the anti-LAG3 antibody heavy chain comprises an amino acid sequence presented in SEQ ID NO: 2, and the variable region of the light chain comprises an amino acid sequence presented in SEQ ID NO: 6; The variable region of the heavy chain of the anti-LAG3 antibody comprises an amino acid sequence presented in SEQ ID NO: 2, and the variable region of the light chain comprises an amino acid sequence presented in SEQ ID NO: 8.

[031] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The amino acid sequence of the variable region of the anti-LAG3 antibody heavy chain is shown in SEQ ID NO: 2, and the amino acid sequence of the variable region of the anti-LAG3 antibody light chain is... Petition 870250099319, dated 10 / 30 / 2025, page 28 / 80 19 / 52 presented in SEQ ID NO: 4; The amino acid sequence of the variable region of the anti-LAG3 antibody heavy chain is shown in SEQ ID NO: 2, and the amino acid sequence of the variable region of the anti-LAG3 antibody light chain is shown in SEQ ID NO: 6; The amino acid sequence of the variable region of the anti-LAG3 antibody heavy chain is shown in SEQ ID NO: 2, and the amino acid sequence of the variable region of the anti-LAG3 antibody light chain is shown in SEQ ID NO: 8.

[032] In some embodiments of the present disclosure, anti-LAG3 antibody or antigen-binding fragment thereof is provided, wherein the anti-LAG3 antibody or antigen-binding fragment thereof is selected from Fab, Fab', F(ab')2, Fd, Fv, dAb, a complementarity-determining region fragment, a single-chain antibody, a humanized antibody, and a chimeric antibody.

[033] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The anti-LAG3 antibody comprises a non-CDR region derived from a human antibody.

[034] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The anti-LAG3 antibody comprises a constant region derived from human antibody; Preferably, the anti-LAG3 antibody comprises the constant region selected from a constant region of IgG1, IgG2, IgG3, or IgG4. Petition 870250099319, dated 10 / 30 / 2025, page 29 / 80 20 / 52 human.

[035] In some embodiments of this disclosure, the anti-LAG3 antibody or its antigen-binding fragment is provided, wherein: The constant region of the anti-LAG3 antibody heavy chain is the C region of the Ig gamma-1 chain (e.g., as established in SEQ ID NO: 18) or the C region of the Ig gamma-4 chain (e.g., as established in SEQ ID NO: 20), and the constant region of the light chain is the C region of the Ig kappa chain (e.g., as established in SEQ ID NO: 19).

[036] Amino acid sequence of the constant region of the IgG1 heavy chain: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDK KVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV SHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 18).

[037] In some embodiments of the present disclosure, the anti-LAG3 antibody is of human origin Subtype IgG1 and, according to the EU numbering system, the constant region of the antibody heavy chain has the following mutations: L234A and L235A; L234A and G237A; L235A and G237A; or L234A, L235A and G237A.

[038] In some forms of carrying out this disclosure, the Petition 870250099319, dated 10 / 30 / 2025, p. 30 / 80 21 / 52 anti-LAG3 antibody is of the human IgG4 subtype and, according to the EU numbering system, the constant region of the antibody heavy chain presents the following mutations: F234A and L235A; F234A and G237A; L235A and G237A; or F234A, L235A and G237A.

[039] In this disclosure, the letters before the position number represent amino acids before the mutation, and the letters after the position number represent amino acids after the mutation, unless otherwise specified. In some embodiments of this disclosure, according to the EU numbering system, the constant region of the immunoglobulin heavy chain also has one or more mutations selected from: N297A, D265A, D270A, P238D, L328E, E233D, H268D, P271G, A330R, C226S, C229S, E233P, P331S, S267E, L328F, A330L, M252Y, S254T, T256E, N297Q, P238S, P238A, A327Q, A327G, P329A, K322A, T394D, G236R, G236A, L328R, A330S, P331S, H268A, E318A and K320A.

[040] In some embodiments of the present disclosure, the anti-LAG3 antibody is a monoclonal antibody.

[041] In some embodiments of the present disclosure, the anti-LAG3 antibody is an immunoglobulin.

[042] In some embodiments of the present disclosure, the anti-LAG3 antibody is a single-chain antibody.

[043] Another aspect of the present disclosure relates to an antibody-drug conjugate (ADC), comprising an antibody or an antigen-binding fragment thereof, and a small molecule drug, wherein the antibody or the antigen-binding fragment thereof Petition 870250099319, dated 10 / 30 / 2025, p. 31 / 80 22 / 52 is any anti-LAG3 antibody or antigen-binding fragment thereof, as described in the present invention; preferably, the small molecule drug is a small molecule cytotoxic drug or a cellular agonist; more preferably, the small molecule drug is a tumor chemotherapeutic drug, and the cellular agonist is an immune cell agonist, such as a T cell agonist or an NK cell agonist.

[044] The chemotherapeutic drug may be a conventional chemotherapeutic drug for tumors, such as an alkylating agent, an antimetabolite, an antitumor antibiotic, a plant-derived anticancer drug, a hormone, an immunomodulator, etc.

[045] In some embodiments of the present disclosure, an antibody-drug conjugate is provided, in which the anti-LAG3 antibody or its antigen-binding fragment is linked to a small molecule drug by means of a ligand; the ligand may be a ligand known to experts in the field, such as a hydrazone linkage, a disulfide linkage or a peptide linkage.

[046] In some embodiments of the present disclosure, the antibody-drug conjugate is provided, wherein the molar ratio of the anti-LAG3 antibody or antigen-binding fragment to the small molecule drug is 1:(2-4), such as 1:2, 1:3 or 1:4.

[047] Another aspect of this disclosure relates to an isolated nucleic acid molecule, in which the isolated nucleic acid molecule encodes either of the anti-LAG3 antibodies or the antigen-binding fragment thereof described in this disclosure.

[048] Another aspect of the present disclosure relates to a recombinant vector comprising the nucleic acid molecule isolated from the present disclosure.

[049] Another aspect of this disclosure relates to a cell Petition 870250099319, dated 10 / 30 / 2025, p. 32 / 80 23 / 52 host comprising the isolated nucleic acid molecule of the present disclosure or the recombinant vector of the present disclosure.

[050] Another aspect of the present disclosure relates to a method for preparing the anti-LAG3 antibody or the antigen-binding fragment thereof, according to any of the present disclosures, comprising a step of culturing the host cell under suitable conditions and recovering the anti-LAG3 antibody or the antigen-binding fragment from a cell culture.

[051] Another aspect of the present disclosure relates to a pharmaceutical composition, comprising any anti-LAG3 antibody or antigen-binding fragment thereof described in the present disclosure, or any antibody-drug conjugate described in the present disclosure; optionally, it further comprises a pharmaceutically acceptable excipient.

[052] Another aspect of this disclosure relates to a combined product comprising a first product and a second product packaged separately, wherein the first product comprises the anti-LAG3 antibody or the antigen-binding fragment thereof or the antibody-drug conjugate, in accordance with this disclosure; and the second product comprises at least one anti-PD1 antibody or one anti-CD73 antibody; Preferably, the first product and the second product independently comprise one or more pharmaceutically acceptable excipients; Ideally, the combined product also includes a package insert.

[053] In some embodiments of this disclosure, the combined product is provided, in which: Petition 870250099319, dated 10 / 30 / 2025, page 33 / 80 24 / 52 the molar ratio of the anti-LAG3 antibody or the antigen-binding fragment thereof to the anti-PD-1 antibody or the anti-CD73 antibody is between (1:5) and (5:1), for example, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1 or 5:1.

[054] In some embodiments of the present disclosure, the combined product, wherein the anti-CD73 antibody is any of the anti-CD73 antibodies mentioned above.

[055] Another aspect of the present disclosure relates to the anti-LAG3 antibody or the antigen-binding fragment thereof or to antibody-drug conjugates, according to any embodiment of the present disclosure, which are intended for use in the treatment or prevention of a tumor or anemia; Preferably, the tumor is one or more tumors selected from the group consisting of ovarian cancer, esophageal cancer, melanoma, hematological malignancy, glioblastoma, renal cell carcinoma, lung cancer, prostate cancer, bladder cancer, colon cancer, rectal cancer, liver cancer, gastric cancer, breast cancer, brain cancer, pancreatic cancer, thyroid cancer, head and neck cancer, and renal cancer; Preferably, lung cancer is non-small cell lung cancer; Preferredly, the hematological neoplasm is leukemia; Preferably, esophageal cancer is squamous cell carcinoma of the esophagus.

[056] Anti-LAG3 antibody or antigen-binding fragment thereof or antibody-drug conjugates are provided, according to any embodiment of this disclosure, for use in the treatment or prevention of a tumor or anemia; Preferably, the tumor is one or more tumors selected from the group consisting of ovarian cancer, esophageal cancer, melanoma, Petition 870250099319, dated 10 / 30 / 2025, page 34 / 80 25 / 52 hematological neoplasm, glioblastoma, renal cell carcinoma, lung cancer, prostate cancer, bladder cancer, colon cancer, rectal cancer, liver cancer, gastric cancer, breast cancer, brain cancer, pancreatic cancer, thyroid cancer, head and neck cancer, and kidney cancer; Preferably, lung cancer is non-small cell lung cancer; Preferredly, the hematological neoplasm is leukemia; Preferably, esophageal cancer is squamous cell carcinoma of the esophagus.

[057] Another aspect of the present disclosure relates to a method for treating or preventing a tumor or anemia, comprising a step of administering to a needy individual an effective amount of the anti-LAG3 antibody or the antigen-binding fragment thereof or any of the antibody-drug conjugates of the present disclosure, according to any of the embodiments of the present disclosure; Preferably, the tumor is one or more selected from the group consisting of ovarian cancer, esophageal cancer, melanoma, hematological malignancy, glioblastoma, renal cell carcinoma, lung cancer, prostate cancer, bladder cancer, colon cancer, rectal cancer, liver cancer, gastric cancer, breast cancer, brain cancer, pancreatic cancer, thyroid cancer, head and neck cancer, and kidney cancer; Preferably, lung cancer is non-small cell lung cancer; Preferredly, the hematological neoplasm is leukemia; Preferably, esophageal cancer is squamous cell carcinoma of the esophagus.

[058] In one or more embodiments of the present disclosure, a method is provided for treating or preventing a tumor, wherein: Petition 870250099319, dated 10 / 30 / 2025, page 35 / 80 26 / 52 The anti-LAG3 antibody is administered in a single dose of 0.1100 mg per kg of body weight, preferably 1-15 mg, 1-12 mg, 1-10 mg (e.g., 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg or 10 mg) or 6-10 mg per kg of body weight; or the anti-LAG3 antibody is administered to each individual in a single dose of 10-1000 mg (for example, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg or about 1000 mg), preferably 50-500 mg, 100-400 mg, 150-300 mg, 150-250 mg or 200 mg; Ideally, administration is performed once every 3 days, 4 days, 5 days, 6 days, 10 days, 1 week, 2 weeks, or 3 weeks; Preferably, one route of administration is intravenous infusion by drip or intravenous injection.

[059] In some embodiments, anti-LAG3 antibody administration is performed in 2-week (14-day) or 3-week (21-day) cycles, and preferably, anti-LAG3 antibody is administered intravenously on the first day (D1) of each cycle. For example, anti-LAG3 antibody is administered once every two weeks (q2w) or three weeks (q3w).

[060] However, it should be noted that the total daily dose of the drug (e.g., the pharmaceutical composition) or the pharmaceutically active ingredient (e.g., the anti-LAG3 antibody or its antigen-binding fragment) of this disclosure should be determined by an attending physician within the scope of reliable medical judgment. For each specific patient, the specific therapeutically effective dose level is determined based on a variety of factors, including the specific type and severity of the tumor to be treated, the formulation form. Petition 870250099319, dated 10 / 30 / 2025, page 36 / 80 27 / 52 specific to the drug used, the patient's age, body weight, general health status, sex and diet, administration time, route of administration, excretion rate, duration of treatment, other drugs used concomitantly and similar factors well known in the medical field. For example, practice in the technique involves starting administration at dose levels below those necessary to achieve the desired therapeutic effect and gradually increasing the dose until the desired effect is achieved.

[061] In this publication, unless otherwise defined, the scientific and technical terms used herein have the meanings generally understood by those skilled in the art. Furthermore, the laboratory operations of cell culture, molecular genetics, nucleic acid chemistry, and immunology used herein are routine procedures widely used in their respective fields. For a better understanding of this publication, definitions and explanations of related terms are provided below.

[062] As used herein, the term EC50 refers to the concentration for 50% of the maximum effect, that is, the concentration that can cause 50% of the maximum effect.

[063] As used herein, the term antibody refers to an immunoglobulin molecule that generally consists of two pairs of polypeptide chains (each pair with a light chain (L) and a heavy chain (H)). Antibody light chains are classified into κ and λ light chains. Heavy chains are classified into μ, δ, γ, α, or ε. Antibody isotypes are defined as IgM, IgD, IgG, IgA, and IgE. In the light and heavy chains, the variable region and the constant region are linked by a J region of about 12 or more amino acids, and the heavy chain further comprises a D region of about 3 or more amino acids. Each heavy chain consists of a Petition 870250099319, dated 10 / 30 / 2025, p. 37 / 80 28 / 52 variable heavy chain (VH) region and a constant heavy chain (CH) region. The constant heavy chain region consists of 3 domains (CH1, CH2, and CH3). Each light chain consists of a variable light chain (VL) region and a constant light chain (CL) region. The constant light chain region consists of a CL domain. The antibody's constant region can mediate the binding of immunoglobulins to tissues or host factors, including the binding of various immune system cells (e.g., effector cells) to the first component (C1q) of the classical complement system. The VH and VL regions can be subdivided into hypervariable regions (called complementarity-determining regions (CDRs)), among which conservative regions called structure regions (FRs) are distributed. Each VH and VL consists of 3 CDRs and 4 FRs arranged from the amino terminal to the carboxyl terminal in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.The variable regions (VH and VL) of each heavy chain / light chain pair form an antibody binding site. The assignment of amino acids to the regions or domains is based on Bethesda Md, Kabat Sequences of Proteins of Immunological Interest (National Institutes of Health, (1987 and 1991)), or Chothia & Lesk J. Mol. Biol., 1987; 196: 901-917; Chothia et al., Nature, 1989; 342: 878883, or on the definition of the IMGT numbering system, see the definition in Ehrenmann F, Kaas Q, Lefranc MP, IMGT / 3Dstructure-DB and IMGT / DomainGapAlign: a database and tool for immunoglobulins or antibodies, T-cell receptors, MHC, IgSF and MhcSF[J]., Nucleic acids research, 2009; 38(suppl_1): D301-D307.

[064] The term “antibody” is not limited to any specific method of antibody production. For example, antibody includes recombinant antibody, monoclonal antibody, and polyclonal antibody. Antibody may be composed of antibodies of different isotypes, such as IgG (e.g., subtype IgG1, IgG2, IgG3, or IgG4), IgA1, IgA2, IgD, IgE, or IgM. Petition 870250099319, dated 10 / 30 / 2025, p. 38 / 80 29 / 52

[065] As used herein, the terms “mAb” and “monoclonal antibody” refer to an antibody or antibody fragment derived from a group of highly homologous antibodies, that is, from a group of antibody molecules identical except for natural mutations that may occur spontaneously. The monoclonal antibody is highly specific for a single epitope on an antigen. The polyclonal antibody, in relation to the monoclonal antibody, generally comprises at least two or more different antibodies that generally recognize different epitopes on an antigen. Monoclonal antibodies can generally be obtained using hybridoma technology, first reported by Kohler et al. (Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity [J]. Nature, 1975; 256(5517): 495), but can also be obtained using recombinant DNA technology (see, for example, U.S. Patent 4,816,567).

[066] As used herein, the term “humanized antibody” refers to an antibody or antibody fragment obtained when all or part of the CDR regions of a human immunoglobulin (recipient antibody) are replaced by the CDR regions of a non-human antibody (donor antibody), wherein the donor antibody may be a non-human antibody (e.g., mouse, rat, or rabbit) with expected specificity, affinity, or reactivity. In addition, some amino acid residues in the structural regions (FRs) of the recipient antibody may also be replaced by amino acid residues from the corresponding non-human antibodies or by amino acid residues from other antibodies to further improve or optimize antibody performance. For more details on humanized antibodies, see, for example, Jones et al., Nature, 1986; 321: 522-525; Reichmann et al., Nature, 1988; 332: 323-329; Presta, Curr. Op. Struct. Biol., 1992; 2: 593-596; and Clark, Immunol.Today, 2000; 21: 397-402. Petition 870250099319, dated 10 / 30 / 2025, page 39 / 80 30 / 52

[067] As used in this document, the term “isolate” refers to obtaining it by artificial means from a natural state. If a particular “isolated” substance or component is present in nature, it may have been altered from its natural environment, or it may have been isolated from the natural environment, or both. For example, a particular non-isolated polynucleotide or polypeptide occurs naturally in a particular living animal, and the same polynucleotide or polypeptide with high purity isolated from such a natural state is termed an isolated polynucleotide or polypeptide. The term “isolate” does not exclude the existence of artificial or synthetic substances or other impurities that do not affect the activity of the substance.

[068] As used in this document, the term “vector” refers to a nucleic acid carrier into which a polynucleotide can be inserted. When a vector allows the expression of the protein encoded by the inserted polynucleotide, the vector is called an expression vector. The vector can be introduced into a host cell by transformation, transduction, or transfection, so that the elements of the genetic substance carried by the vector can be expressed in the host cell. Vectors are well known to specialists in the field, including, among others: plasmids; phagemids; cosmids; artificial chromosomes, such as yeast artificial chromosome (YAC), bacterial artificial chromosome (BAC), or P1-derived artificial chromosome (PAC); phages, such as λ phages or M13 phages; and animal viruses.Animal viruses that can be used as vectors include, but are not limited to, retroviruses (including lentiviruses), adenoviruses, adeno-associated viruses, herpesviruses (such as herpes simplex virus), poxviruses, baculoviruses, papillomaviruses, and papovaviruses (such as SV40). A vector may comprise a variety of elements that control expression, including, but are not limited to, a promoter sequence, a transcription initiation sequence, an enhancer sequence, a selection element, and a reporter gene. Furthermore, the vector... Petition 870250099319, dated 10 / 30 / 2025, page 40 / 80 31 / 52 may also include a replication initiation site.

[069] As used in this document, the term “host cell” refers to cells into which vectors can be introduced, including, but not limited to, prokaryotic cells such as E. coli or Bacillus subtilis, fungal cells such as yeast or Aspergillus cells, insect cells such as Drosophila S2 or Sf9 cells, or animal cells such as fibroblasts, CHO cells, GS cells, COS cells, NSO cells, HeLa cells, BHK cells, HEK 293 cells, or human cells.

[070] As used in this document, the term “specific binding” refers to a non-random binding reaction between two molecules, such as a reaction between an antibody and an antigen to which it is directed. In some embodiments, an antibody that binds specifically to an antigen (or an antibody that is specific for an antigen) means that the antibody binds to the antigen with an affinity (KD) less than about 10⁻⁵ M, for example, less than about 10⁻⁶ M, 10⁻⁷ M, 10⁻⁸ M, 10⁻⁹ M or 10⁻¹⁰ M or less.

[071] As used in this document, the term “KD” refers to a dissociation equilibrium constant for a specific antibody-antigen interaction and is used to describe the binding affinity between the antibody and the antigen. A smaller dissociation equilibrium constant indicates a stronger antibody-antigen binding and a higher affinity between the antibody and the antigen. Generally, antibodies bind to antigens (e.g., PD-1 protein) with a dissociation equilibrium constant (KD) less than about 10⁻⁵ M, such as less than about 10⁻⁶ M, 10⁻⁷ M, 10⁻⁸ M, 10⁻⁹ M, or 10⁻¹⁰ M or less. KD can be determined using methods known to experts in the field, for example, using a Fortebio molecular interaction instrument.

[072] As used herein, the terms monoclonal antibody and Petition 870250099319, dated 10 / 30 / 2025, page 41 / 80 32 / 52 mAb have the same meaning and are used interchangeably; the terms polyclonal antibody and pAb have the same meaning and are used interchangeably. Furthermore, in this disclosure, amino acids are generally represented by one- or three-letter abbreviations known in the field. For example, alanine may be represented by A or Ala.

[073] As used in this document, the term “pharmaceutically acceptable carrier and / or excipient” refers to a carrier and / or excipient that is pharmacologically and / or physiologically compatible with the subject and the active ingredient, which is well known in the art (see, for example, Remington's Pharmaceutical Sciences. Edited by Gennaro AR, 19th ed. Pennsylvania: Mack Publishing Company, 1995) and includes, among others, pH regulators, surfactants, adjuvants, and ionic strength enhancers. For example, pH regulators include, among others, phosphate buffer; surfactants include, among others, cationic, anionic, or non-ionic surfactants such as Tween-80; ionic strength enhancers include, among others, sodium chloride.

[074] As used herein, the term “effective amount” refers to an amount sufficient to obtain, or at least partially obtain, a desired effect. For example, a prophylactically effective amount against a disease (e.g., a tumor) refers to an amount sufficient to prevent, stop, or delay the development of the disease (e.g., a tumor); a therapeutically effective amount refers to an amount sufficient to cure or at least partially stop the disease and its complications in patients suffering from the disease. It is undoubtedly within the competence of specialists in the field to determine such an effective amount. For example, the effective amount for therapeutic purposes will depend on the severity of the disease to be treated, the general state of the patient's immune system, the patient's general condition such as age, body weight, and sex, and the route of administration. Petition 870250099319, dated 10 / 30 / 2025, page 42 / 80 33 / 52 administration and other treatments administered concomitantly, etc.

[075] As used herein, when referring to the amino acid sequence of lymphocyte activation gene 3 (LAG3), this includes the full length of the LAG3 protein, or the LAG3 ECD extracellular fragment of LAG3, or a fragment comprising LAG3 ECD, and also includes a full-length fusion protein of the LAG3 protein or a fusion protein of LAG3 ECD, such as a fragment fused to a mouse or human IgG Fc protein fragment (mFc or hFc). However, those skilled in the art will understand that mutations or variations (including, but not limited to, substitutions, deletions, and / or additions) can be produced naturally or artificially introduced in the amino acid sequence of the LAG3 protein without affecting its biological functions. Therefore, in the present disclosure, the term LAG3 or LAG3 protein shall include all such sequences, including their natural or artificial variants.Furthermore, when describing a sequence fragment of the LAG3 protein, the corresponding sequence fragments in their natural or artificial variants are also included.

[076] In this disclosure, the terms “first” (e.g., first product) and “second” (e.g., second product) are used for purposes of distinction or clarity of expression and do not have typical sequential meanings unless otherwise specified. Beneficial Effects of This Disclosure

[077] This disclosure achieves one or more of the following effects: (1) The anti-LAG3 antibody in this disclosure has superior affinity and specificity; (2) The anti-LAG3 antibody of the present disclosure can effectively block the interaction between LAG3 and MHC-II, thus specifically alleviating LAG3 immunosuppression in an organism; Petition 870250099319, dated 10 / 30 / 2025, page 43 / 80 34 / 52 (3) The antibody in this disclosure can effectively treat or prevent tumors. Brief Description of the Figures

[078] Figure 1: Results of assays for the binding activity of H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) to the human antigen LAG3mG1Fc by ELISA.

[079] Figure 2: Results of assays for the binding activity of H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) to human LAG3 antigen on the surface of the 293T-LAG3 cell by FACS.

[080] Figure 3: Results of assays for H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) competing with MHC II antigen on the Raji cell membrane surface for binding to human LAG3-mG1Fc by competitive flow cytometry.

[081] Figure 4: Results of assays for the biological activity of anti-LAG3 antibodies in promoting IFN-γ secretion by mixed lymphocyte reaction (MLR).

[082] Figure 5: Results of assays for the biological activity of anti-LAG3 antibodies in promoting IL-2 secretion by mixed lymphocyte reaction (MLR).

[083] Figure 6: Results of assays for the biological activity of anti-LAG3 antibodies in blocking the interaction between LAG3 and MHC-II. Detailed Description of the Invention

[084] The embodiments of this disclosure will be described in detail below, with reference to examples. Experts in the field will understand that the following examples are for illustrative purposes only and should not be construed as limiting the scope of this disclosure. Examples where specific technologies or conditions are not specified are carried out in accordance with the technologies. Petition 870250099319, dated 10 / 30 / 2025, page 44 / 80 35 / 52 or conditions described in publications in the field (for example, see Molecular Cloning: A Laboratory Manual, by J. Sambrook et al. and translated by Huang Peitang et al., third edition, Science Press) or as directed in the package insert. The reagents or instruments used are conventional, commercially available products unless their manufacturers are specified.

[085] The positive control antibody, Relatlimab, has sequences referenced to U.S. Patent Publication No. US20160326248A1, wherein, for the heavy chain amino acid sequence, see SEQ ID NO: 1 of this patent publication, and for the light chain amino acid sequence, see SEQ ID NO: 2 of this patent publication. Relatlimab is an anti-LAG3 antibody.

[086] Amino acid sequence of the Relatlimab heavy chain: QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDYYWNWIRQPPG KGLEWIGEINHRGSTNSNPSLKSRVTLSLDTSKNQFSLKLRSVTAADTAVYYC AFGYSDYEYNWFDPWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALG CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 23).

[087] Amino acid sequence of the Relatlimab light chain: EIVLTQSPATLSLSPGERATLSCRASQSISSYLAWYQQKPGQAP RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTF GQGTNLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC (SEQ ID NO: 24). Petition 870250099319, dated 10 / 30 / 2025, page 45 / 80 36 / 52

[088] The antibody 14C12H1L1(hG1TM) is an anti-PD-1 antibody prepared by Akeso Biopharma Inc.

[089] Amino acid sequence of the heavy chain of 14C12H1L1(hG1TM): EVQLVESGGGLVQPGGSLRLSCAASGFAFSSYDMSWVRQAPG KGLDWVATISGGGRYTYYPDSVKRFTISRDNSKNNLYLQMNSLRAEDTALYY CANRYGEAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 21).

[090] Amino acid sequence of the 14C12H1L1(hG1TM) light chain: DIQMTQSPSSMSASVGDRVTFTCRASQDINTYLSWFQQKPGKS PKTLIYRANRLVSGVPSRFSGSGSGQDYTLTISSLQPEDMATYYCLQYDEFPL TFGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC (SEQ ID NO: 22).

[091] Amino acid sequence of human LAG3-mG1Fc: LQPGAEVPVVWAQEGAPAQLPCSPTIPLQDLSLLRRAGVTWQH QPDSGPPAAPGHPLAPGPPHPAAPSSWGPRPRRYTVLSVGPGGLRSGRLPL QPRVQLDERGRQRGDFSLWLRPARRADAGEYRAAVHLRDRALSCRLLRLRG QASMTASPPGSLRASDWVILNCSFSRPDRPASVHWFRNRGQGRVPVRESPH HHLAESFLFLPQVSPMDGSGPWGCILTRYDGFNVSIMYNLTVLGLEPPTPLTVY AGAGSRVGLPCRLPAGVGTRSFLTAKWTPPGGGPDLLVTGDNGDFTLRLED VSQAQAGTYTCHIHLQEQQLNATVTLAITVTPKSFGSPGSLGKLLCEVTPVSG Petition 870250099319, de 30 / 10 / 2025, pág. 46 / 80 37 / 52 QERFVWSSLDTPSQRSFSGPWLEAQEAQLLSQPWQCQLYQGERLLGAAVYF TELSSPGAQRSGRAPGALPGHLKLENLYFQGPRGPTIKPCPPCKCPAPNLL GGPSVFIPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISWFVNNVEVHTAQT QTHREDYNSTLRVVSALPIQHQDWMSGKEFCKVNNKDLPAPIERTISKPKGS VRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNYKNT EPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTP GK (SEQ ID NO: 25).

[092] The 293T-LAG3 cell line was constructed by Akeso Biopharma Inc. The 293T-LAG3 cell line was produced by viral infection of HEK293T cells using 3rd Generation Lentivirus Systems (see, for example, A Third Generation Lentivirus Vector with a Conditional Packaging System. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D and Naldini L., J Virol., 1998. 72(11): 8463-8471), where the lentivirus expression vector used was plenti6.3 / V5-huLAG3FL-BSD (LAG3, Gene Bank ID: NP_002277.4; plenti6.3 / V5-BSD vector, acquired from Invitrogen, Cat. No. K531520).

[093] The Raji-PDL1 cell line was constructed by Akeso Biopharma Inc. The Raji-PDL1 cell line was produced by viral infection of Raji cells using 3rd Generation Lentiviral Systems (see, for example, A Third Generation Lentivirus Vector with a Conditional Packaging System. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D and Naldini L., J Virol., 1998. 72(11): 8463-8471), where the lentivirus expression vector used was plenti6.3 / V5-PDL1 (PDL1, Genebank ID: NP_054862.1; plenti6.3 / V5 vector, acquired from Invitrogen, Cat. No. K5315-20).

[094] The Jurkat-NFAT-PD1-LAG3 cell line was constructed by Akeso Biopharma Inc. The Jurkat-NFAT-PD1-LAG3 cell line was produced by viral infection of PD-1 effector cells (CPM, manufacturer: Promega, Cat. No. J112A) using third-generation lentiviral systems (see, for example, A Petition 870250099319, dated 10 / 30 / 2025, page 47 / 80 38 / 52 Third Generation Lentivirus Vector with a Conditional Packaging System. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D and Naldini L., J Virol., 1998. 72(11): 8463-8471), in which the lentivirus expression vector used was pCDHhuLAG3FL-RFP-NEO (LAG3, Genebank ID: NP_002277.4; vector pCDH-CMVMCS-EF1-RFP+Neo, acquired from Youbio, Cat. No. VT9005). Example of Preparation 1: Design and Preparation of AntiLAG3 Antibodies 1. Antibody design

[095] The inventors creatively designed a series of antibody sequences based on the known sequence of the LAG3 protein (NCBI Reference Sequence: NP_002277.4), its three-dimensional crystal structure, etc. Through extensive screening and testing, humanized monoclonal antibodies that bind specifically to LAG3 were finally obtained, named H9L8, H9L9, and H9L10, respectively. The amino acid sequences of the variable regions of the heavy and light chains of the monoclonal antibodies and their coding sequences are as follows.

[096] Nucleotide sequence of the variable region of the H9v heavy chain of H9L8 (360 bp): CAGGTGCAGCTGCAGCAGTGGGGAGCTGGACTGCTGAAACC TAGCGAGACACTGAGCCTGACCTGTGCTGTGTACGGCGGATCTATCAGCG ATTACTACTGGAACTGGATCAGGCAGCCCCCTGGAAAGGGACTGGAATGG ATCGGAGAGATCAACTACAGGGCACCACCAACTCCAATCCCTCTCTGAA GAGCAGGGTGACACTGAGCCTCGACACAAGCAAGAATCAGTTCAGCCTGA AGCTGAGGTCCGTGACCGCTGCTGATACAGCTGTGTACTACTGTGCCTTC GGCTACAGCGATTACGAGTACGATTGGTTCGACCCTTGGGGCCAGGGAAC ACTGGTTACAGTGAGCTCC (SEQ ID NO: 1).

[097] Amino acid sequence of the variable region of the H9v heavy chain of H9L8 (120 aa): Petition 870250099319, dated 10 / 30 / 2025, p. 48 / 80 39 / 52 QVQLQQWGAGLLKPSETLSLTCAVYGGSISDYYWNWIRQPPGK GLEWIGEINYRGTTNSNPSLKSRVTLSLDTSKNQFSLKLRSVTAADTAVYYCAF GYSDYEYDWFDPWGQGTLVTVSS (SEQ ID NO: 2).

[098] Nucleotide sequence of the variable region of the L8v light chain of H9L8 (321 bp): GAGATCGTTCTGACCCAGAGCCCAGCTACACTGAGCCTGTCT CCTGGAGAGAGGGCTACACTGTCCTGCAGAGCTAGCCAGACCATCAGCA GCTACCTGGCTTGGTACCAGCAGAAGCCTGGCCAAGCTCCAAGGCTGCTG ATCTACGACGCCTCTAATAGGGCCACCGGCATCCCTGCTAGATTCTCTGG AAGCGGCAGCGGAACCGACTTTACACTGACAATCAGCTCCCTGGAGCCCG AGGATTTCGCTGTTTACTACTGTCAGCAGCGCAGCAACTGGCCCATCACAT TCGGACAGGGCACAAATCTGGAGATCAAG (SEQ ID NO: 3).

[099] Amino acid sequence of the variable region of the L8v light chain of H9L8 (107 aa): EIVLTQSPATLSLSPGERATLSCRASQTISSYLAWYQQKPGQAP RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITF GQGTNLEIK (SEQID NO: 4).

[0100] The nucleotide sequence of the variable region of the H9v heavy chain of H9L9 is identical to the nucleotide sequence of the variable region of the H9v heavy chain of H9L8, as established in SEQ ID NO: 1.

[0101] The amino acid sequence of the variable region of the H9v heavy chain of H9L9 is identical to the amino acid sequence of the variable region of the H9v heavy chain of H9L8, as established in SEQ ID NO: 2.

[0102] Nucleotide sequence of the variable region of the L9v light chain of H9L9 (321 bp): GAGATCGTTCTGACCCAGAGCCCAGCTACACTGAGCCTGTCT CCTGGAGAGAGGGCTACACTGTCCTGCAGAGCTAGCCAGACCATCAGCA GCTACCTGGCTTGGTACCAGCAGAAGCCTGGCCAAGCTCCAAGGCTGCTG Petition 870250099319, dated 10 / 30 / 2025, p. 49 / 80 40 / 52 ATCTACGACGGCTCTAATAGGGCCACCGGCATCCCTGCTAGATTCTCTGG AAGCGGCAGCGGAACCGACTTTACACTGACAATCAGCTCCCTGGAGCCCG AGGATTTCGCTGTTTACTACTGTCAGCAGCGCAGCAACTGGCCCCTCACAT TCGGACAGGCACAAATCTGGAGATCAAG (SEQ ID NO: 5).

[0103] Amino acid sequence of the variable region of the L9v light chain of H9L9 (107 bp): EIVLTQSPATLSLSPGERATLSCRASQTISSYLAWYQQKPGQAP RLLIYDGSNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTF GQGTNLEIK (SEQ ID NO: 6).

[0104] The nucleotide sequence of the variable region of the H9v heavy chain of H9L10 is identical to the nucleotide sequence of the variable region of the H9v heavy chain of H9L8, as established in SEQ ID NO: 1.

[0105] The amino acid sequence of the variable region of the H9v heavy chain of H9L10 is identical to the amino acid sequence of the variable region of the H9v heavy chain of H9L8, as established in SEQ ID NO: 2.

[0106] Nucleotide sequence of the variable region of the L10v light chain of H9L10 (321 bp): GAGATCGTTCTGACCCAGAGCCCAGCTACACTGAGCCTGTCT CCTGGAGAGAGGGCTACACTGTCCTGCAGAGCTAGCCAGTCCATCAGCAG CTACCTGGCTTGGTACCAGCAGAAGCCTGGCCAAGCTCCAAGGCTGCTGA TCTACGACGGCTCTAATAGGGCCACCGGCATCCCTGCTAGATTCTCTGGA AGCGGCAGCGGAACCGACTTTACACTGACAATCAGCTCCCTGGAGCCCGA GGATTTCGCTGTTTACTACTGTCAGCAGCGCAGCAACTGGCCCATCACATT CGGACAGGGCACAAATCTGGAGATCAAG (SEQ ID NO: 7).

[0107] Amino acid sequence of the variable region of the L10v light chain of H9L10 (107 bp): EIVLTQSPATLSLSPGERATLSCRASQSISSYLAWYQQKPGQAP RLLIYDGSNRATGIPARFSGGSSGTDFTLTISSLEPEDFAVYYCQQRSNWPITF Petition 870250099319, dated 10 / 30 / 2025, pp. 50 / 80 41 / 52 GQGTNLEIK (SEQ ID NO: 8).

[0108] The amino acid sequences of the H9L8 antibody CDRs are as follows (according to the IMGT numbering system): HCDR1: GGSISDYY (SEQ ID NO: 9); HCDR2: INYRGTT (SEQ ID NO: 10); HCDR3: AFGYSDYEYDWFDP (SEQ ID NO: 11); LCDR1: QTISSY (SEQ ID NO: 12); LCDR2: DAS (SEQ ID NO: 13); LCDR3: QQRSNWPIT (SEQ ID NO: 14).

[0109] The amino acid sequences of the H9L9 antibody CDRs are as follows (according to the IMGT numbering system): HCDR1: GGSISDYY (SEQ ID NO: 9); HCDR2: INYRGTT (SEQ ID NO: 10); HCDR3: AFGYSDYEYDWFDP (SEQ ID NO: 11); LCDR1: QTISSY (SEQ ID NO: 12); LCDR2: DGS (SEQ ID NO: 15); LCDR3: QQRSNWPLT (SEQ ID NO: 16).

[0110] The amino acid sequences of the antibody CDRs H9L10 are as follows (according to the IMGT numbering system): HCDR1: GGSISDYY (SEQ ID NO: 9); HCDR2: INYRGTT (SEQ ID NO: 10); HCDR3: AFGYSDYEYDWFDP (SEQ ID NO: 11); LCDR1: QSISSY (SEQ ID NO: 17); LCDR2: DGS (SEQ ID N°: 15); LCDR3: QQRSNWPIT (SEQ ID NO: 14). 2. Expression and purification of humanized antibodies H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT)

[0111] The heavy chain cDNA sequences (the sequences Petition 870250099319, dated 10 / 30 / 2025, pp. 51 / 80 42 / 52 variable region encoders are presented in SEQ ID NO: 1; The constant regions were the C regions of the gamma-4 chain of Ig) of H9L8(hG4WT), H9L9(hG4WT), and H9L10(hG4WT); the cDNA sequence of the light chain (the coding sequence of the variable region is shown in SEQ ID NO: 3; the constant region was the C region of the kappa chain of human Ig) of H9L8(hG4WT); the cDNA sequence of the light chain (the coding sequence of the variable region is shown in SEQ ID NO: 5; the constant region was the C region of the kappa chain of human Ig) of H9L9(hG4WT); and the cDNA sequence of the light chain (the coding sequence of the variable region is shown in SEQ ID NO: 7; the constant region was the C region of the kappa chain of human Ig) of H9L10(hG4WT) were cloned separately into pUC57simple vectors (provided by GenScript), and the plasmids pUC57simple-H9, pUC57simple-L8, pUC57simple-L9, and pUC57simple-L10 were obtained, respectively.The pUC57simple-H9, pUC57simple-L8, pUC57simple-L9, and pUC57simple-L10 plasmids were digested (HindIII and EcoRI). The heavy and light chains isolated by electrophoresis were subcloned separately into pcDNA3 vectors, and the recombinant plasmids were extracted for cotransfection into 293F cells. After 7 days of cell culture, the culture solution was separated by high-speed centrifugation, and the supernatant was concentrated and loaded onto a HiTrap MabSelect SuRe column. The protein was eluted in a single step with an elution buffer. The target sample was isolated, and the buffer was exchanged in PBS.

[0112] Amino acid sequence of the constant region of the heavy chain of H9L8(hG4WT), H9L9(hG4WT) or H9L10(hG4WT): ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDK RVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYK Petition 870250099319, dated 10 / 30 / 2025, page 52 / 80 43 / 52 CKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSC SVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 20).

[0113] Amino acid sequence of the constant region of the light chain of H9L8(hG4WT), H9L9(hG4WT) or H9L10(hG4WT): RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC (SEQ ID NO: 19). Example of Preparation 2: Preparation of Human Anti-Lysozyme Antibody from Chicken Eggs

[0114] The human anti-chicken egg lysozyme IgG antibody sequence (anti-HEL, or human IgG, abbreviated as hIgG) was derived from the variable region sequence of the Fab F10.6.6 sequence in the study reported by Acierno et al., entitled Affinity maturation enhances stability and plasticity of the Fv domain of anti-protein antibodies (Acierno et al., J Mol Biol., 2007; 374(1): 130-46). The preparation method was as follows: Nanjing GenScript Biotech was tasked with performing amino acid codon optimization and gene synthesis on heavy and light chain genes (complete sequence or variable region) of the human IgG antibody. Consulting the standard technologies presented in the Handbook of Molecular Cloning: A Laboratory Manual (Third Edition) and using standard molecular cloning techniques such as PCR, enzymatic digestion, DNA gel extraction, ligation transformation, colony PCR, or identification by enzymatic digestion, the heavy and light chain genes were subcloned into the antibody heavy chain expression vector and the antibody light chain expression vector of the mammalian expression system, respectively. The heavy and light chain genes of the recombinant expression vectors were subsequently sequenced and analyzed. After the Petition 870250099319, dated 10 / 30 / 2025, page 53 / 80 44 / 52 verification of sequence correctness, a medium or large quantity of endotoxin-free expression plasmids was prepared, and heavy and light chain expression plasmids were transiently co-transfected into HEK293 cells for recombinant antibody expression. After 7 days of culture, cell culture solutions were collected and subjected to affinity purification on an rProtein A (GE) column, and the quality of the resulting antibody sample was determined using standard SDS-PAGE and SEC-HPLC analytical techniques. Example 1: Anti-LAG3 Antibody Binding Activity Assays for Antigen by ELISA

[0115] An ELISA plate was coated with 2 μg / mL of human LAG3mG1Fc and incubated overnight at 4 °C. The antigen-coated ELISA plate was then washed once with PBST and blocked with a PBS solution containing 1% BSA (blocking solution) at 37 °C for 2 h. After blocking, the ELISA plate was washed 3 times with PBST. Serially diluted antibodies with PBST solution (dilution gradients for the antibodies are shown in Table 1) were added. The ELISA plate containing the test antibodies was incubated at 37 °C for 30 min and then washed 3 times with PBST. After washing, a working solution of HRP-labeled goat anti-human IgG (H+L) secondary antibody (Jackson, Cat. No. 109-035-088), diluted 1:5000, was added, and the plate was then incubated at 37 °C for 30 min. After incubation, the plate was washed 4 times with PBST.Color development was then performed with TMB (Neogen, 308177) in the dark for 5 min, and a stopping solution was added to interrupt the color development reaction. The ELISA plate was immediately placed in a microplate reader, and the OD at a wavelength of 450 nm in each well of the ELISA plate was measured. The data were analyzed and processed using SoftMax Pro software. Petition 870250099319, dated 10 / 30 / 2025, pp. 54 / 80 45 / 52 6.2.1.

[0116] The results of the test are presented in Table 1 and Figure 1. Table 1. Results of H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) binding assays to human antigen LAG3-mG1 Fc by ELISA. LAG3-mG1Fc human, 2 pg / mL, 50 pL / well Antibody dilution (pg / mL) H9L8 (hG4WT) H9L9 (hG4WT) H9L10 (hG4WT) Relatlimab 1 2.403 2.463 2.485 2.555 2.438 2.471 2.568 2.589 0.3 2.414 2.399 2.420 2.412 2.345 2.419 2.468 2.557 0.1 2.201 2.141 2.200 2.135 2.121 2.107 2.260 2.327 0.03 1.734 1.647 1.783 1.691 1.637 1.657 1.868 1.975 0.01 1.104 1.065 1.089 1.054 1.019 1.018 1.220 1.288 0.003 0.592 0.558 0.567 0.560 0.525 0.540 0.649 0.725 0.001 0.282 0.277 0.298 0.287 0.275 0.282 0.324 0.344 0 0.122 0.123 0.125 0.118 0.121 0.126 0.119 0.121 Secondary IgG antibody against goat anti-human (H+L), HRP (1:5000) EC50(nM) 0.123 0.129 0.140 0.097

[0117] The results show that: H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) were able to bind effectively to the human antigen LAG3-mG1Fc in a dose-dependent manner and exhibited binding activity comparable to that of the positive control antibody Relatlimab. Example 2: Assays for Anti-LAG3 Antibody Binding Activity to Human LAG3 Antigen on the Cell Surface by Cell Cytometry Flow

[0118] Antibody labeling and flow cytometry detection: 293T-LAG3 cells expressing the human LAG3 antigen were digested with conventional pancreatin, and the number of cells in each collection tube was 3 χ Petition 870250099319, dated 10 / 30 / 2025, pp. 55 / 80 46 / 52 105. LAG3 antibody dilutions prepared using 1% PBSA (PBS containing 1% BSA) at final concentrations of 0.0123 nM, 0.123 nM, 1.23 nM, 3.7 nM, 11.1 nM, 33.3 nM, 100 nM, and 300 nM, respectively, were incubated with 293T-LAG3 cells expressing LAG3 on ice for 1 h. After centrifugation and repeated washing with 1% PBSA, 100 μL of FITC goat anti-IgG antibody (purchased from Jackson, Cat. No. 109-095-098) (diluted 1:300) were added to each tube, and the mixture was incubated on ice in the dark for 40 minutes. After washing with 1% PBSA, 200 μL of 1% PBSA were added to resuspend the cells. Fluorescence signals were detected using the FITC channel in a flow cytometer. The results of the binding of humanized anti-LAG3 antibodies to 293T-LAG3 cells are shown in Figure 2. The EC50 values ​​for the binding of anti-LAG3 antibodies to the antigen on the surface of 293TLAG3 cells are shown in Table 2. Table 2. Results of assays for the binding activity of anti-LAG3 antibodies to the antigen on the surface of 293T-LAG3 cells by flow cytometry. Antibody EC50(nM) Relatlimab 4.289 H9L8(hG4WT) 4.862 H9L9(hG4WT) 4.525 H9L10(hG4WT) 3.925

[0119] As can be seen in Table 2, the anti-LAG3 antibodies were able to bind effectively to the target LAG3 protein on the surface of the 293T-LAG3 cell, and the binding activity of the anti-LAG3 antibodies H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) to the antigen on the surface of the 293T-LAG3 cell was comparable to that of the positive control antibody Relatlimab. Example 3: Assays for Anti-LAG3 Antibodies Competing with MHC II on the Raji Cell Membrane Surface for Binding to Human LAG3mGIFc Antigen by Competitive Flow Cytometry

[0120] Raji Cells (medium: 1640 + 10% SFB) (Resource Center) Petition 870250099319, dated 10 / 30 / 2025, pp. 56 / 80 47 / 52 Cells (from the Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Cat. No. TCHu 44) were added to EP tubes at a rate of 300,000 cells per sample. 1000 μL of 1% PBSA (PBS containing 1% BSA) was added. The mixture was centrifuged at 600 χ²g for 5 min, and the supernatant was discarded. 100 μL of hIgG1 (prepared by Akeso Biopharma Inc., Lot No. 20190410) at a final concentration of 300 nM were added to each tube, and the mixture was incubated on ice for 1 h; 200 μL of 1% PBSA were added to the Raji cells after incubation, and the mixture was centrifuged at 600 χ²g for 5 min, followed by removal of the supernatant. According to the experimental design, antibodies diluted to the corresponding concentrations were added to additional clean EP tubes at 60 μL / tube. 60 μL of human LAG3-mG1Fc (prepared by Akeso Biopharma Inc.)(Lot No. 20190508) were added to each corresponding antibody tube, and the mixture was thoroughly mixed and pre-incubated on ice for 30 min, so that the final antibody concentrations were 300 nM, 100 nM, 33.3 nM, 11.1 nM, 3.7 nM, 1.23 nM, 0.123 nM, and 0.0123 nM. The final concentration of human LAG3-mG1Fc was 3 nM. 100 μL of the pre-incubated antibody and protein mixture were added to the cells. The resulting mixture was thoroughly mixed and incubated on ice in the dark for 1 h; 200 μL of 1% PBSA were added, and the mixture was centrifuged at 600 χ²g for 5 min, followed by removal of the supernatant, and then the pellet was washed twice; 100 μL of an anti-mouse APC antibody (acquired from Biolegend, Cat.No. 405308) (diluted in a 1:400 ratio) were added, and the mixture was thoroughly mixed and incubated on ice in the dark for 40 min; 200 μL of 1% PBSA were added, and the mixture was centrifuged at 600 χ²g for 5 min, followed by removal of the supernatant; 200 μL of 1% PBSA were added to each tube to resuspend the cells, and then the suspension was transferred to a sample loading tube for analysis in a flow cytometer. The results are shown in Figure 3 and Table 3. Petition 870250099319, dated 10 / 30 / 2025, pp. 57 / 80 48 / 52 fluorescence analysis and curve fitting, the EC50 values ​​for competitive binding of the antibodies Relatlimab, H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) were calculated as 1.153 nM, 1.459 nM, 1.482 nM and 1.435 nM, respectively. Table 3. Results of the fluorescence intensity analysis of Relatlimab, H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) in the competition. With MHC II on the surface of the Raji cell for binding to the human antigen LAG3-mG1Fc by FACS. Antibody EC50(nM) Relatlimab 1.153 H9L8(hG4WT) 1.459 H9L9(hG4WT) 1.482 H9L10(hG4WT) 1.435

[0121] The results show that the H9L8(hG4WT) antibodies, H9L9(hG4WT) and H9L10(hG4WT) were able to competitively bind to LAG3 and effectively block LAG3 binding to MHC II on the surface of Raji cells in a dose-dependent manner, exhibiting activity comparable to that of the positive control antibody Relatlimab. Example 4: Assays for the biological activity of anti-LAG3 antibodies in promoting IFN-Γ and IL-2 secretion by mixed lymphocyte reaction (MLR) 1. Assays for the biological activity of anti-LAG3 antibodies in promoting IFN-Γ secretion in the Raji-PDLI mixed lymphocyte reaction system.

[0122] Raji-PDL1 cells were conventionally subcultured. PBMCs (from healthy donors) were thawed, cultured in 10 mL of complete medium 1640, and stimulated with SEB (staphylococcal enterotoxin B) (Dianotech, Cat. No. S010201) at 0.5 μg / mL for two days. Raji-PDL1 cells were treated with MMC (Stressmarq, Cat. No. SIH-246-10MG) at a working concentration of 2 μg / mL and incubated at 37 °C in a 5% CO2 incubator for 1 h; PBMCs stimulated with SEB for 2 days and cells Petition 870250099319, dated 10 / 30 / 2025, pp. 58 / 80 49 / 52 Raji-PDL1 cells treated with MMC for 1 h were collected, washed twice with PBS, and then resuspended in complete medium (i.e., RPMI 1640 + 10% FBS) and counted. PBMCs and Raji-PDL1 cells were added separately to a 96-well U-shaped plate (Corning, Model No. 3799) at 10 * 10⁴ cells / well and co-cultured. According to the experimental design, antibodies (final concentrations of each antibody were 300 nM, 30 nM, and 3 nM when used alone or in combination) were added and co-cultured with the cells in an incubator for 3 days; after 3 days, the cells were centrifuged at 250 * g for 5 min, and the cell culture supernatant was collected and analyzed for IFN-γ by ELISA.

[0123] As shown in Figure 4, the mixed culture of human PBMCs and Raji-PDL1 cells promoted IFN-γ secretion in PBMCs, and the addition of antibodies to the mixed culture system can significantly induce additional IFN-γ secretion in PBMCs. In terms of the level of activity in promoting IFN-γ secretion, the anti-LAG3 antibodies H9L8(hG4WT), H9L9(hG4WT), and H9L10(hG4WT), each in combination with 14C12H1L1(hG1TM), and the positive control antibody Relatlimab in combination with 14C12H1L1(hG1TM), were all able to promote IFN-γ secretion, with comparable activities. 2. Assays for the biological activity of anti-LAG3 antibodies in promoting IL-2 secretion in the RAJI-PDL1 mixed lymphocyte reaction system.

[0124] Raji-PDL1 cells were conventionally subcultured. PBMCs were thawed, cultured in 10 mL of complete medium 1640, and stimulated with SEB (staphylococcal enterotoxin B, acquired from Dianotech, Cat. No. S010201) at 0.5 μg / mL for two days. Raji-PDL1 cells were treated with MMC (Stressmarq, Cat. No. SIH-246-10MG) at a working concentration of 2 μg / mL and incubated at 37 °C in a 5% CO2 incubator for 1 h. PBMCs stimulated with SEB for 2 days and the cells Petition 870250099319, dated 10 / 30 / 2025, pp. 59 / 80 50 / 52 Raji-PDL1 cells treated with MMC for 1 h were collected, washed twice with PBS, and then resuspended in complete medium (i.e., RPMI 1640 + 10% FBS) and counted. PBMCs and Raji-PDL1 cells were added separately to a 96-well U-shaped plate (Corning, Model No. 3799) at 10 x 10⁴ cells / well and co-cultured. According to the experimental design, antibodies (final concentrations of each antibody were 300 nM, 30 nM, and 3 nM when used alone or in combination) were added and co-cultured with the cells for 3 days; after 3 days, the cells were centrifuged at 250 x g for 5 min, and the cell culture supernatant was collected and analyzed for IL-2 by ELISA.

[0125] As shown in Figure 5, the mixed culture of human PBMCs (from healthy donors) and Raji-PDL1 cells promoted IL-2 secretion in PBMCs to some extent, and the addition of antibodies to the mixed culture system could significantly induce additional IL-2 secretion in PBMCs, exhibiting a significant dose-dependent relationship. In terms of the level of activity in promoting IL-2 secretion, the anti-LAG3 antibodies H9L8(hG4WT), H9L9(hG4WT), and H9L10(hG4WT), each in combination with 14C12H1L1(hG1TM), and the positive control antibody Relatlimab in combination with 14C12H1L1(hG1TM), could all promote IL-2 secretion, with comparable activities. Example 5: Assays for Evaluating the Biological Activity of Anti-LAG3 Antibodies in Blocking the Interaction between LAG3 and MHC-II (Reporter Gene Method)

[0126] Jurkat-NFAT-PD1-LAG3 cells and Raji cells were used as a reporter gene system. After the addition of a SEE superantigen, a TCR-NFAT signaling pathway was activated to induce luciferase expression. LAG3 in Jurkat cells bound to MHC-II in Raji cells, so that the NFAT signaling pathway was inhibited and the expression of Petition 870250099319, dated 10 / 30 / 2025, pages 60 / 80 51 / 52 luciferase was downregulated. The antibody, by specifically binding to LAG3, relieved the inhibition and increased luciferase expression.

[0127] Jurkat-NFAT-PD1-LAG3 cells and Raji cells (acquired from the Cell Resource Center, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Cat. No. TCHu 44) were collected and centrifuged at 110 xg for 5 min, followed by removal of the supernatant. The cells were then resuspended in a 1640 + 10% FBS medium and counted. Jurkat-NFAT-PD1-LAG3 cells were seeded in a 96-well black-bottom plate (Corning, Model No. 3916) at 105 cells / well (30 μL / well); According to the experimental design, antibodies (at final concentrations of 0.3 nM, 3 nM, and 300 nM) were added at 10 μL / well, and the mixture was pre-incubated at 37 °C in a 5% CO2 incubator for 30 min. Meanwhile, SEE (Staphylococcal Enterotoxins E, acquired from Toxin Technology, Cat. No. ET404) (at a final concentration of 0.05 ng / mL) was added to Raji cells, and the mixture was incubated at 37 °C in a 5% CO2 incubator for 30 min.After 30 min, SEE-treated Raji cells were added to the 96-well plate containing Jurkat-NFAT-PD1-LAG3 cells described above at 2 x 10⁴ cells / well (40 μL / well), with the final volume of each well being 80 μL. The mixture was thoroughly mixed and incubated at 37 °C in a 5% CO₂ incubator for 6 h. After incubation, the culture plate was removed and allowed to reach room temperature. The Bright-Glo™ Luciferase Assay System (purchased from Promega, Cat. No. E2650) was added at 80 μL / well, and the mixture was incubated in the dark for 2 min. Then, URL values ​​were read. The hG4WT(hIgG4) isotypic control was produced by Akeso Biopharma Inc., Lot No. 20190910.

[0128] As shown in Figure 6, the anti-LAG3 antibodies H9L8(hG4WT), H9L9(hG4WT), H9L10(hG4WT) and the positive control antibody Relatlimab were able to block the interaction between LAG3 and MHC-II and, Petition 870250099319, dated 10 / 30 / 2025, pp. 61 / 80 52 / 52 thus, increase luciferase expression, and the activities of the anti-LAG3 antibodies H9L8(hG4WT), H9L9(hG4WT) and H9L10(hG4WT) were superior to those of the control antibody Relatlimab.

[0129] Although the specific embodiments of this disclosure have been described in detail, those skilled in the art will understand that various modifications and substitutions may be made to these details in accordance with all the teachings disclosed, and all such changes will fall within the scope of protection of this disclosure. The full scope of this disclosure is provided by the appended claims and any equivalents thereof. Petition 870250099319, dated 10 / 30 / 2025, pp. 62 / 80

Claims

1 / 11 Claims 1. ANTI-LAG3 ANTIBODY or an antigen-binding fragment thereof, characterized in that the anti-LAG3 antibody comprises a variable heavy chain region and a variable light chain region, wherein the variable heavy chain region comprises HCDR1, HCDR2 and HCDR3, and the variable light chain region comprises LCDR1, LCDR2, LCDR3, wherein: HCDR1 comprises an amino acid sequence presented in SEQ ID NO: 9, HCDR2 comprises an amino acid sequence presented in SEQ ID NO: 10, HCDR3 comprises an amino acid sequence presented in SEQ ID NO: 11; LCDR1 comprises an amino acid sequence presented in SEQ ID NO: 12 or SEQ ID NO: 17, LCDR2 comprises an amino acid sequence presented in SEQ ID NO: 13 or SEQ ID NO: 15, LCDR3 comprises an amino acid sequence presented in SEQ ID NO: 14 or SEQ ID NO:

16.

2. ANTI-LAG3 ANTIBODY or the antigen-binding fragment thereof, according to claim 1, characterized by: LCDR1 comprising an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprising an amino acid sequence shown in SEQ ID NO: 13, and LCDR3 comprising an amino acid sequence shown in SEQ ID NO: 14; or LCDR1 comprising an amino acid sequence shown in Petition 870250099319, dated 10 / 30 / 2025, page 1.63 / 80 2 / 11 in SEQ ID NO: 12, LCDR2 comprising an amino acid sequence shown in SEQ ID NO: 15 and LCDR3 comprising an amino acid sequence shown in SEQ ID NO: 16; or LCDR1 comprising an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprising an amino acid sequence shown in SEQ ID NO: 15, and LCDR3 comprising an amino acid sequence shown in SEQ ID NO: 14; or LCDR1 comprising an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprising an amino acid sequence shown in SEQ ID NO: 13; and LCDR3 comprising an amino acid sequence shown in SEQ ID NO: 16; or LCDR1 comprising an amino acid sequence shown in SEQ ID NO: 12, LCDR2 comprising an amino acid sequence shown in SEQ ID NO: 15; and LCDR3 comprise an amino acid sequence shown in SEQ ID NO: 14; or LCDR1 comprise an amino acid sequence presented in Petition 870250099319, dated 10 / 30 / 2025, page 1.64 / 80 3 / 11 in SEQ ID NO: 17, LCDR2 comprising an amino acid sequence shown in SEQ ID NO: 13; and LCDR3 comprising an amino acid sequence shown in SEQ ID NO: 14; or LCDR1 comprising an amino acid sequence shown in SEQ ID NO: 17, LCDR2 comprising an amino acid sequence shown in SEQ ID NO: 13; and LCDR3 comprising an amino acid sequence shown in SEQ ID NO: 16; or LCDR1 comprising an amino acid sequence shown in SEQ ID NO: 17; LCDR2 comprising an amino acid sequence shown in SEQ ID NO: 15; and LCDR3 comprising an amino acid sequence shown in SEQ ID NO:

16.

3. ANTI-LAG3 ANTIBODY or the antigen-binding fragment thereof, according to any one of claims 1 to 2, characterized by: the amino acid sequence of LCDR1 being presented in SEQ ID NO: 12, the amino acid sequence of LCDR2 being presented in SEQ ID NO: 13 and the amino acid sequence of LCDR3 being presented in SEQ ID NO: 14; Petition 870250099319, dated 10 / 30 / 2025, p.65 / 80 4 / 11 or by the amino acid sequence of LCDR1 being shown in SEQ ID NO: 12, by the amino acid sequence of LCDR2 being shown in SEQ ID NO: 15 and by the amino acid sequence of LCDR3 being shown in SEQ ID NO: 16; or by the amino acid sequence of LCDR1 being shown in SEQ ID NO: 17; by the amino acid sequence of LCDR2 being shown in SEQ ID NO: 15, and by the amino acid sequence of LCDR3 being shown in SEQ ID NO: 14; or by the amino acid sequence of LCDR1 being shown in SEQ ID NO: 12; by the amino acid sequence of LCDR2 being shown in SEQ ID NO: 13; and by the amino acid sequence of LCDR3 being shown in SEQ ID NO: 16; or by the amino acid sequence of LCDR1 being shown in SEQ ID NO: 12; by the amino acid sequence of LCDR2 being shown in SEQ ID NO: 15; and because the amino acid sequence of LCDR3 is shown in SEQ ID NO: 14; Petition 870250099319, dated 10 / 30 / 2025, p.66 / 80 5 / 11 or by the amino acid sequence of LCDR1 being shown in SEQ ID NO: 17, by the amino acid sequence of LCDR2 being shown in SEQ ID NO: 13, and by the amino acid sequence of LCDR3 being shown in SEQ ID NO: 14; or by the amino acid sequence of LCDR1 being shown in SEQ ID NO: 17, by the amino acid sequence of LCDR2 being shown in SEQ ID NO: 13, and by the amino acid sequence of LCDR3 being shown in SEQ ID NO: 16; or by the amino acid sequence of LCDR1 being shown in SEQ ID NO: 17, by the amino acid sequence of LCDR2 being shown in SEQ ID NO: 15, and by the amino acid sequence of LCDR3 being shown in SEQ ID NO:

16.

4. ANTI-LAG3 ANTIBODY or the antigen-binding fragment thereof, according to any one of claims 1 to 3, characterized by: the variable region of the anti-LAG3 antibody heavy chain comprising an amino acid sequence presented in SEQ ID NO: 2, and the variable region of the anti-LAG3 antibody light chain comprising an amino acid sequence presented in SEQ ID NO: 4; Petition 870250099319, dated 10 / 30 / 2025, p. 67 / 80 6 / 11 the variable region of the anti-LAG3 antibody heavy chain comprising an amino acid sequence presented in SEQ ID NO: 2, and the variable region of the anti-LAG3 antibody light chain comprising an amino acid sequence presented in SEQ ID NO: 6; or by the variable region of the heavy chain of the anti-LAG3 antibody comprising an amino acid sequence presented in SEQ ID NO: 2, and the variable region of the light chain of the anti-LAG3 antibody comprising an amino acid sequence presented in SEQ ID NO:

8.

5. ANTI-LAG3 ANTIBODY or the antigen-binding fragment thereof, according to any one of claims 1 to 4, characterized by: the amino acid sequence of the variable region of the heavy chain of the anti-LAG3 antibody being presented in SEQ ID NO: 2, and the amino acid sequence of the variable region of the light chain of the anti-LAG3 antibody being presented in SEQ ID NO: 4; the amino acid sequence of the variable region of the heavy chain of the anti-LAG3 antibody being presented in SEQ ID NO: 2, and the amino acid sequence of the variable region of the light chain of the anti-LAG3 antibody being presented in SEQ ID NO: 6; or the amino acid sequence of the variable region of the heavy chain of the anti-LAG3 antibody being presented in SEQ ID NO: 2, and the amino acid sequence of the variable region of the light chain of the anti-LAG3 antibody being presented in SEQ ID NO:

8.

6. ANTI-LAG3 ANTIBODY or antigen-binding fragment thereof, according to any one of claims 1 to 5, characterized in that the anti-LAG3 antibody or antigen-binding fragment thereof is selected from Fab, Fab', F(ab')2, Fd, Fv, dAb, a fragment of the complementarity-determining region, a single-chain antibody, a humanized antibody and a chimeric antibody.

7. ANTI-LAG3 ANTIBODY or the antigen-binding fragment thereof, according to any one of claims 1 to 6, characterized in that the anti-LAG3 antibody comprises a non-CDR region derived from a human antibody; preferably, in that the constant region of the anti-LAG3 antibody is derived from a human antibody; preferably, in that the constant region of the anti-LAG3 antibody is selected from a constant region of human IgG1, IgG2, IgG3 or IgG4; in that the constant region of the heavy chain of the anti-LAG3 antibody is the C region of the gamma-1 chain of Ig (for example, as set forth in SEQ ID NO: 18) or the C region of the gamma-4 chain of Ig (for example, as set forth in SEQ ID NO: 20), and the constant region of the light chain is the C region of the kappa chain of Ig (for example, as set forth in SEQ ID NO: 19).

8. ANTI-LAG3 ANTIBODY or the antigen-binding fragment thereof, according to any one of claims 1 to 7, characterized in that the anti-LAG3 antibody is of the human IgG1 subtype and, according to the EU numbering system, the constant region of the antibody heavy chain has the following mutations: L234A and L235A; L234A and G237A; L235A and G237A; or L234A, L235A and G237A; or the anti-LAG3 antibody is of the human IgG4 subtype, Petition 870250099319, dated 30 / 10 / 2025, p. 69 / 80 8 / 11 and, according to the EU numbering system, the constant region of the antibody heavy chain has the following mutations: F234A and L235A; F234A and G237A; L235A and G237A; or F234A, L235A and G237A.

9. Antibody-drug conjugate, characterized by comprising an antibody or an antigen-binding fragment thereof and a small molecule drug, wherein the antibody or antigen-binding fragment thereof is the antibody or antigen-binding fragment thereof as defined in any one of claims 1 to 8; preferably, the small molecule drug is a small molecule cytotoxic drug or a cell agonist; more preferably, the small molecule drug is a chemotherapeutic drug for tumors, and the cell agonist is an agonist for immune cells, such as an agonist for T cells or NK cells.

10. Antibody-drug conjugate, according to claim 9, characterized in that: the anti-LAG3 antibody or the antigen-binding fragment thereof is linked to the small molecule drug by means of a linker; for example, the linker is a hydrazone linkage, a disulfide linkage or a peptide linkage; preferably, wherein the molar ratio of the anti-LAG3 antibody or the antigen-binding fragment thereof to the small molecule drug is 1:(2-4).

11. ISOLATED NUCLEIC ACID MOLECULE, characterized by the isolated nucleic acid molecule encoding the anti-LAG3 antibody, as defined in any one of claims 1 to 8. Petition 870250099319, dated 10 / 30 / 2025, pp. 70 / 80 9 / 11 12. Recombinant VECTOR, characterized by comprising the isolated nucleic acid molecule, as defined in claim 11.

13. HOST CELL, characterized by comprising the isolated nucleic acid molecule, as defined in claim 11, or the recombinant vector, as defined in claim 12.

14. METHOD FOR PREPARING ANTI-LAG3 ANTIBODY or its antigen-binding fragment, as defined in any one of claims 1 to 8, characterized by comprising the step of culturing the host cell, as defined in claim 13, under suitable conditions and recovering the anti-LAG3 antibody or its antigen-binding fragment from a cell culture.

15. PHARMACEUTICAL COMPOSITION, characterized by comprising the anti-LAG3 antibody or the antigen-binding fragment thereof, as defined in any one of claims 1 to 8, or the antibody-drug conjugate, as defined in any one of claims 9 to 10; wherein, optionally, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

16. COMBINED PRODUCT, characterized by comprising a first product and a second product packaged separately, wherein the first product comprises an anti-LAG3 antibody or the antigen-binding fragment thereof, as defined in any of claims 1 to 8, or an antibody-drug conjugate, as defined in any of claims 9 to 10; and the second product comprises at least one anti-PD1 antibody or an anti-CD73 antibody; preferably, the first product and the second product independently comprise one or more pharmaceutically acceptable excipients; Petition 870250099319, dated 10 / 30 / 2025, pp. 71 / 80 10 / 11 preferably, the combined product further comprises a package insert.

17. COMBINED PRODUCT, according to claim 16, characterized in that the molar ratio of the anti-LAG3 antibody or the antigen-binding fragment thereof to the anti-PD-1 antibody or the anti-CD73 antibody is from (1:5) to (5:1).

18. USE OF ANTI-LAG3 ANTIBODY or antigen-binding fragment thereof, as defined in any one of claims 1 to 8, or of the antibody-drug conjugate, as defined in any one of claims 9 to 10, characterized in that it is in the preparation of a medicament for the treatment or prevention of a tumor; preferably, the tumor is one or more selected from the group consisting of ovarian cancer, esophageal cancer, melanoma, hematological malignancy, glioblastoma, renal cell carcinoma, lung cancer, prostate cancer, bladder cancer, colon cancer, rectal cancer, liver cancer, gastric cancer, breast cancer, brain cancer, pancreatic cancer, thyroid cancer, head and neck cancer and renal cancer; preferably, the lung cancer is non-small cell lung cancer; preferably, the hematological malignancy is leukemia; preferably, the esophageal cancer is squamous cell carcinoma of the esophagus.

19. ANTI-LAG3 ANTIBODY or the antigen-binding fragment thereof, according to any one of claims 1 to 8, or the antibody-drug conjugate, according to any one of claims 9 to 10, characterized in that it is for use in the treatment or prevention of a tumor; preferably, the tumor is one or more tumors selected from the group consisting of ovarian cancer, esophageal cancer, melanoma, hematologic neoplasm, glioblastoma, renal cell carcinoma, lung cancer, prostate cancer, bladder cancer, colon cancer, rectal cancer, liver cancer, gastric cancer, breast cancer, brain cancer, pancreatic cancer, thyroid cancer, head and neck cancer and renal cancer; preferably, the lung cancer is non-small cell lung cancer; Preferably, hematological neoplasm is leukemia; preferably, esophageal cancer is squamous cell carcinoma of the esophagus.

20. METHOD FOR TREATING OR PREVENTING A TUMOR, characterized by comprising the step of administering to a needy individual an effective amount of the anti-LAG3 antibody or the antigen-binding fragment thereof, as defined in any one of claims 1 to 8, or the antibody-drug conjugate, as defined in any one of claims 9 to 10; preferably, the tumor is one or more selected from the group consisting of ovarian cancer, esophageal cancer, melanoma, hematological malignancy, glioblastoma, renal cell carcinoma, lung cancer, prostate cancer, bladder cancer, colon cancer, rectal cancer, liver cancer, gastric cancer, breast cancer, brain cancer, pancreatic cancer, thyroid cancer, head and neck cancer, and renal cancer; preferably, the lung cancer is non-small cell lung cancer; preferably, the hematological malignancy is leukemia;Preferably, esophageal cancer is squamous cell carcinoma of the esophagus. Petition 870250099319, dated 10 / 30 / 2025, pp. 73 / 80;

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